Antifungal Activity of Resveratrol Derivatives against Candida Species

trans-Resveratrol (1a) is a phytoalexin produced by plants in response to infections by pathogens. Its potential activity against clinically relevant opportunistic fungal pathogens has previously been poorly investigated. Evaluated herein are the candidacidal activities of oligomers (2a, 3-5) of la purified from Vitis vinifera grape canes and several analogues (1b-1j) of la obtained through semisynthesis using methylation and acetylation. Moreover, trans-epsilon-viniferin (2a), a dimer of la, was also subjected to methylation (2b) and acetylation (2c) under nonselective conditions. Neither the natural oligomers of la (2a, 3-5) nor the derivatives of 2a were active against Candida albicans SC5314. However, the dimethoxy resveratrol derivatives Id and le exhibited antifungal activity against C. albicans with minimum inhibitory concentration (MIC) values of 29-37 mu g/mL and against 11 other Candida species. Compound le inhibited the yeast-to-hyphae morphogenetic transition of C. albicans at 14 mu g/mL.